Methods of inhibiting cerebral inflammation

Abstract

The present invention provides methods of inhibiting cerebral inflammation comprising administering a CCR5 inhibitor to a subject.

1 . A method of inhibiting cerebral inflammation in a subject, said method comprising administering a CCR5 inhibitor to a subject, wherein the CCR5 inhibitor is a polypeptide comprising an N-terminal portion and a C-terminal portion, wherein the N-terminal portion comprises the signature sequence QGP[P or L] and the C-terminal portion comprises an amino acid sequence at least 70% identical to SEQ ID NO: 1. 
     
     
         2 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the signature sequence is QGP[P or L][L or G or S or M][M or D or S or Q or G]. 
     
     
         7 . The method of  claim 1 , wherein the signature sequence is QGP[P or L][L or G or S or M][M or D or S or Q or G]XX[Q or G or L or A or T or S]X, wherein X denotes any natural or modified amino acid. 
     
     
         8 . The method of  claim 1 , wherein the signature sequence is QGP[P or L]LM or QGPPG[D or S]. 
     
     
         9 . The method of  claim 1 , wherein the signature sequence is QGPPLM or QGPPGD. 
     
     
         10 . The method of  claim 1 , wherein the signature sequence is QGP[P or L][L or M][M or Q][A or W or G or Q or N]X[Q or G or L][S or V or T or G], wherein X denotes any natural or modified amino acid. 
     
     
         11 . The method of  claim 1 , wherein the signature sequence is QGPPLM[A or W][L or T or M][Q or G][S or V or T or G]. 
     
     
         12 . The method of  claim 1 , wherein the signature sequence is QGPP[G or L][M or Q]XX[Q or S][S or V], wherein X denotes any natural or modified amino acid. 
     
     
         13 . The method of  claim 1 , wherein the signature sequence is selected from the group consisting of QGPPLMALQS (SEQ ID NO: 2), QGPPLMWMQV (SEQ ID NO: 3), QGPPLMWLQV (SEQ ID NO: 4), QGPPLMWTQS (SEQ ID NO: 5), QGPPLMWLQT (SEQ ID NO: 6), QGPPLMWTQV (SEQ ID NO: 7), QGPPLMWMQS (SEQ ID NO: 8), QGPPLMATQS (SEQ ID NO: 9), QGPPLMWLQS (SEQ ID NO: 10), QGPPLMALQV (SEQ ID NO: 11), QGPPLMWLGG (SEQ ID NO: 12), QGPPLMWRGS (SEQ ID NO: 13), QGPLLMWLQV (SEQ ID NO: 14), QGPPLMQTTP (SEQ ID NO: 15), QGPPLSWLQV (SEQ ID NO: 30), QGPPLSWLQS (SEQ ID NO: 31), QGPPGQWSQV (SEQ ID NO: 32), QGPPMMAGLS (SEQ ID NO: 33), QGPPLSWQQS (SEQ ID NO: 34), QGPPGMWSQS (SEQ ID NO: 35), QGPPLQWRQS (SEQ ID NO: 36), QGPPLMGTQS (SEQ ID NO: 37), QGPPLMQLQV (SEQ ID NO: 38), QGPPLSWSQV (SEQ ID NO: 39), QGPPMSWSQS (SEQ ID NO: 40), QGPPLMNLQV (SEQ ID NO: 41), QGPPMSAYQV (SEQ ID NO: 42) and QGPPMQGGLS (SEQ ID NO: 43). 
     
     
         14 . The method of  claim 1 , wherein the signature sequence is selected from the group consisting of QGPPLMALQS (SEQ ID NO: 2), QGPPLMWMQV (SEQ ID NO: 3), QGPPLMWLQV (SEQ ID NO: 4), QGPPLMWTQS (SEQ ID NO: 5), QGPPLMWLQT (SEQ ID NO: 6), QGPPLMWTQV (SEQ ID NO: 7), QGPPLMWMQS (SEQ ID NO: 8), QGPPLMATQS (SEQ ID NO: 9), QGPPLMWLQS (SEQ ID NO: 10), QGPPLMALQV (SEQ ID NO: 11), QGPPLMWLGG (SEQ ID NO: 12), QGPPLMWRGS (SEQ ID NO: 13), QGPLLMWLQV (SEQ ID NO: 14) and QGPPLMQTTP (SEQ ID NO: 15). 
     
     
         15 . The method of  claim 1 , wherein the signature sequence is QGPPLMATQS (SEQ ID NO: 9). 
     
     
         16 . The method of  claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 70. 
     
     
         17 . The method of  claim 1 , wherein the subject suffers from a neuroinflammatory disorder that involves cerebral inflammation. 
     
     
         18 . The method of  claim 17 , wherein the neuroinflammatory disorder is Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, viral encephalitis, Rasmussen encephalitis, progressive multifocal leukoencephalopathy (PML) including PML-associated immune reconstitution inflammatory syndrome (IRIS), cerebral malaria, HIV-associated neurocognitive disorders, CNS vasculitis, antibody-mediated inflammatory brain disorders, or neurosarcoidosis. 
     
     
         19 . The method of  claim 18 , wherein the neuroinflammatory disorder disease is multiple sclerosis, Rasmussen's encephalitis, progressive multifocal leukoencephalopathy (PML), PML-associated immune reconstitution inflammatory syndrome (IRIS), cerebral malaria or HIV-associated neurocognitive disorders. 
     
     
         20 . The method of  claim 19 , wherein the neuroinflammatory disorder disease is multiple sclerosis. 
     
     
         21 . (canceled)